Dr. David Shackelford conducts basic translational cancer research and is focused on uncovering the molecular mechanisms driving carcinogenesis, developing new in vitro and in vivo cancer models, and identifying new personalized therapies to treat cancer based on the tumor’s genetic and molecular alterations. His primary expertise is in signal transduction where he utilizes genetically engineered mouse models of lung cancer to study essential growth and survival pathways in non-small cell lung cancer (NSCLC). By integrating molecular biology, immunohistochemistry and micro PET-CT imaging into preclinical studies he has developed a multifaceted, rapid methodology to analyze tumor development and therapeutic response and to identify new therapeutics with the aim of translating bench discoveries into clinical studies.
Selected Cancer-Related Publications:
Shackelford DB, Abt E, Gerken L, Vasquez DS, Seki A, Leblanc M, Wei L, Fishbein MC, Czernin J, Mischel PS, Shaw RJ. LKB1 inactivation dictates therapeutic response of non-small cell lung cancer to the metabolism drug phenformin. Cancer Cell. 2013 Feb 11;23(2):143-58. doi: 10.1016/j.ccr.2012.12.008. Epub 2013 Jan 24.
Egan DF, Shackelford DB, Mihaylova MM, Gelino S, Kohnz RA, Mair W, Vasquez DS, Joshi A, Gwinn DM, Taylor R, Asara JM, Fitzpatrick J, Dillin A, Viollet B, Kundu M, Hansen M, Shaw RJ. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science. 2011 Jan 28;331(6016):456-61. doi: 10.1126/science.1196371. Epub 2010 Dec 23.
Shackelford DB, Shaw RJ. The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat Rev Cancer. 2009 Aug;9(8):563-75. doi: 10.1038/nrc2676.
Shackelford DB, Vasquez DS, Corbeil J, Wu S, Leblanc M, Wu CL, Vera DR, Shaw RJ. mTOR and HIF-1alpha-mediated tumor metabolism in an LKB1 mouse model of Peutz-Jeghers syndrome. Proc Natl Acad Sci U S A. 2009 Jul 7;106(27):11137-42. doi: 10.1073/pnas.0900465106. Epub 2009 Jun 18.
Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A, Vasquez DS, Turk BE, Shaw RJ. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell. 2008 Apr 25;30(2):214-26. doi: 10.1016/j.molcel.2008.03.003.